活性素 I 型受体多态性与肌少症老年人的身体成分：来自 LACE 随机对照试验的分析。
Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.
机构信息
Cardiovascular and Respiratory Interface Section, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom.
Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.
出版信息
PLoS One. 2023 Nov 14;18(11):e0294330. doi: 10.1371/journal.pone.0294330. eCollection 2023.
BACKGROUND
Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia.
METHODS
We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial.
RESULTS
Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone.
CONCLUSION
These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.
背景
衰老与身体成分的变化有关，包括肌肉质量的整体减少和脂肪质量的相应增加。肌少症的特征是肌肉质量和力量的丧失。身体成分和肌肉力量至少部分是由基因决定的，因此，在肌肉生物学中起重要作用的途径（例如，激活素/肌肉生长抑制素信号通路）的多态性被假设为导致肌少症的发展。
方法
我们比较了通过 DXA 测量的区域身体成分，以及通过 PCR 确定的活性 1B 受体 (ACVR1B) 中的两个多态性（rs10783486，次要等位基因频率（MAF）= 0.26 和 rs2854464，MAF = 0.26）在 LACE 试验中来自 110 名患有肌少症的老年人的 DNA 的横断面分析中的基因型。
结果
在该队列中，两种基因型均与肌肉质量或力量无明显关联。对 rs10783486 的初步分析表明，AA/AG 基因型的男性比 GG 男性更高（174±7cm 比 170±5cm，p = 0.023），并且手臂脂肪质量更高（中位数高 15%，p = 0.008），以及腿部脂肪质量（中位数高 14%，p = 0.042）。在调整身高后，手臂脂肪质量仍然显著更高（中位数高 4%，p = 0.024）。女性未观察到相关性（调整或未调整）。对 rs2854464 等位基因的类似分析显示出类似的模式，即存在较小等位基因（GG/AG）与更高的身高相关（GG/AG = 174±7cm 比 AA = 170 ±5cm，p = 0.017）和更高的手臂脂肪质量（中位数高 16%，p = 0.023）。同样，在校正身高后，手臂脂肪量的差异仍然存在。单独分析女性时，未观察到类似的相关性。
结论
这些数据表明，ACVR1B 基因座的多态性变异可能与老年男性的身体成分有关。激活素/肌肉生长抑制素通路可能为预防老年人脂肪堆积提供新的潜在靶点。
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